Alkyloxychloropurin and method of preparing same.



- NITE STATES FRITZ ACH, 0 E MANNHEIM, GERMANY, ASSIGNOR TO- 0. F. BOEHRINGER &

SOEHNE, OF WALDH OF, GERMANY.

ALKYLOXYCHLOROPURIN AND METHOD OF PREPARING SAME.

SPECIFICATION forming part of Letters Patent No. 654,120, dated July 24:, 1900.

Original application filed February 18, 1898, erialNo. 670,847. Divided and this application filed July 22, 1899. Serial No.

724,838. (No specimens.)

To all whom it may concern.-

Be it known that I, FRITZ ACH, a citizen of the Empire of Germany, residing at Mannheim, Germany, have invented certain new and useful Improvements in Alkyl-Oxy-Purins and Methods of Preparing Same; and I do hereby declare the following to be a full, clear, and exact description of the invention, such as will enable others skilled in the art to which it appertains to make and use the same.

This invention relates to the manufacture of alkylized oXy-chloropurins, and in particular to trialkylized oxy-purins.

In carrying out my invention I start from 3-alkyl-chloroxanthins, otherwise known as S-alkyl-8-chloro-26-dioxy-purins, such as 3-methyl-chloroxanthin, which compound, together with its mode of preparation, has been described and claimed in my Letters Patent of the United States No. 631,757, dated August 22, 1899, (of which this is a divisional application,) this 3-alkyl-chloroxanthin being submitted to the action of alkylizing agents in order to obtain the new compounds.

Before proceeding with the specification I will state that I have herein adopted the nomenclature and system of numbering the carbon and nitrogen atoms of the purin-nucleus which has been introduced by Prof. Emil Fischer and described in Berichte der Deutschen Chem'ische n Gesellschaft, Vol. 30, p. 549. According to this system the purinnucleus is arranged and its atoms are numbered thus:

HNCO

oo o u\n oo o-non is 1-3-7-trimethyl-S-chloro-xanthin or 1-3-7- trimethyl-8-chloro-2t dioxy-purin. r In my aforesaid application I have described and claimed generically the method of proceeding from alkyl-uric acids having no alkyl in the position 9, first, to alkylized chloro-xanthins by the agency of phosphorusoxy-chlorid and then from such alkylized chloro-Xanthins to higher alkylized products by alkylization and reduction or vice versa. In that application I have also described and claimed the more specific method of applying the above treatment to 3-alkyl-uric acids and more particularly 3-methyl-uric acid. Among other things I claim in that application the method of preparing 3 -alkyl-chloro- Xanthin and specially S-methyl-chloro-xanthin from 3-methl-uric acid and also the said new compound 3 methyl chloro Xanthin. I

Such matter is therefore not claimed herein; but the invention forming the subject-matter of the present application consists in the preparation of alkylized oXy-chloropurins and specifically 3 methyl 1-7 -diethl-2-6-dioxy-8- chloropurin and also in the method of proceeding from this new compound to a chlorinfree product by reduction and in this new compound itself.

In order to fully disclose my invention, I will first describe the method of preparing the starting material 3-methyl-chloro-Xanthin from 3-methyl-uric acid, it being understood that this method and the resulting compound are not herein claimed, since they form the subject-matter of the claims of my aforesaid application.

Preparation of 3 methyl chloro manthin from -methyZ-uric acicl.0ne part of anhydrous 3-methy1-uric acid is added to five parts, by Volume, of phosphorus-oxy-chlorid and heated under pressure (2. g., in a digester) to from 130 to 140 centigrade and maintained at this temperature for from three to four hours, the mass being steadily agitated. The resulting clear reddish-brown solution is then evaporated in vacuo for the purpose of completely removing the phosphorus-oxy chlo ridt The brownish residue, which has a tough varnish-like consistency, is thereupon brought into solution by boiling the same with about five times its quantity of alcohol or water. The alcoholic solution, which at first is clear, but soon becomes turbid on account of the precipitation of granular crystalline methyl-chloro-xanthin, is boiled for from two to threehours in a reflux condenser andthen allowed to cool. Upon then filtering the methyl-chloro-xanthin remains on the filter as a yellow granular crystalline mass. The filtrate is then evaporated, whereby a second crystallization ensues, resulting in a further yield of the above product, methylchloro-xanthin. The crude product so obtained is brought into solution with dilute alkali, such as two-per-cent. potash lye, treated with animal charcoal or other decolorizing agent, and finally precipitated with dilute sulfuric acid. On cooling the new compound is obtained in the form of yellow-hued coarse crystals, from whose analysis are obtained figures which show the formula of this compound to be G H N,O OI+H O. Its structural formula is found to be:

such formula being established by the fact of the ready conversion of this compound into.

chloro-catfein. (See under II.) I therefore designate this new compound as S-methylchloro-xanthin or 3-methyl-B-chloro-xanthin. The tenaciously-adhering yellow tint, which is very difiicult of removal, has no influence on the percentage composition of the product. Absolute decoloration of the methyl-chloroxanthin may be attained by thoroughly boiling it with a large quantity (thirty parts to one part of the methyl -chloro-xanthin) of acetone. The xanthin is thereby gradually brought into solution, while the adhering coloring matter remains undissolved. Upon cooling, after such solution is eifected, the methyl-chloro-xanth'in crystallizes in anhydrous fine colorless shining foliated crystals or scales. 3-methyl-chloro-Xanthin is soluble in about two hundred and fifty parts boiling water, and on cooling the solution slowly the same crystallizes therefrom in coarse needles, which under the microscope are found to be elongated flat prisms and which contain one molecule of water of crystallization. This water of crystallization escapes on protracted heating at 120 centigrade. It is difficult of solution in boiling alcohol, in acetone, acetic ether, benzene, or chloroform, readily soluble in'dilute alkalies, in ammonia, and soda or potash solutions. It'is equally soluble in concentrated sulfuric acid and fuming hydrochloric acid. From a solution in the latter theoriginal product is precipitated bywater on standing for some time. Heated with chlorin-water or with dilute nitric acid it gives a strong murexid reaction. An ammoniacal solution of the same, added to an ammoniacal silver solution yields a gelatinous silver salt which remains unchanged on boiling. 3 methyl chloroxanthin has no melting-point; but on being rapidly heated it begins to turn yellow at 320 centigrade, and at about 345 centigrade it decomposes with efiervescence. From this body 3-methylchlor Xanthin the new compound 3-methyl-. 1-7- iethyl-2-6- dioxy-8-chloropurin or 3- methyl-diethylchloro-xanthin is made, as follows:

Preparation of 5 methyl 1 7 diethylz-' diary -8- chloropurin from 3-mcthylchlorowcnt7zin.-Bo11r parts, by weight, of 3-methylchloroxanthin are dissolved in twenty-three parts, by volume, of double-normal potashlye (potassium-hydrate solution) and diluted with twenty parts, by volume, of alcohol.

. Six and one-half parts, by weight, of ethyliodid are then added and the whole is boiled for from three to four hours with reflux. The mass is then allowed to cool, when it solidifies in the form of a pulp or fine felted needles.

These are then separated by filtration, redissolved in boiling water and recrystallized therefrom. The fine acicular crystals so obtained have the composition indicated by the formula O H N O Ol, or structurally ex- The reaction to which the formation of the new compound is due proceeds according to the equation:

HN-CO 001 l 0H,.N ON

This new compound with chlorin-water gives astrong murexid reaction. Its melting-point is 136 centigrade. It is moderately soluble in boiling and difficultly soluble in cold water. It dissolves readily in hot alcohol and in cold acetone or chloroform. It is also readily soluble in fuming hydrochloric acid, being precipitated from such solution by water. It will be noted that its structure closely resembles that of chloro-caffein, the only difference being that in lieu of the methyl groups in the positions 1 and 7 in the latter compound it has substituted ethyl groups.

methyl-8-chloro-xanthin or ro-Xanthin or 3-methyl 1-7 1-3-7-trimethyLS-chloro-2-G-didiethyl-8chloro-2-6-dioxypuoxy-purln. rm.

The new trialkyldioXy-chloropurin or trialkyl-chloroxanthin just described may be reduced to a chlorin-free compound by the following method:

Preparation of -methyl-1-7-diethyl-2-$-diowy-purin.-This new body is obtained by reduction of 3-methyl-1-7-diethyl-2-6-dioxy-8- chloropurin or 3-methyl-1-7-diethyl-S-chloro- Xanthimwhich has been described under head 11 If one part, by weight, of this chloro- Xanthin be heated with ten parts, by weight,of fuming hydriodic acid to centigrade, solution is speedily effected. The heating is then continued on a boiling-Water bath so long until,with the addition of phosphonium-iodid in sufficient quantity to take up the liberated iodin,a clear solution is formed. This solution is then evaporated to dryness, and the crystalline residue is taken up with water and supersaturated with alkali. Through this treatment the new base separates as a colorless oil, which very soon congeals, forming fine acicular crystals. The base is then extracted With a suitable vehicle, such as chloroform or ether, whereupon the extract is evaporated and the colorless residue recrystallized from benzene. From the benzene solution,to which ligroin is preferably added, the 3-methyl 1-7- diethyl-2-6-dioxypurin crystallizes in the form of splendidly developed vitreous colorless prisms whose analysis gives figures which correspond well to the formula O H N O The structural formula of the base is:

The reducing process is expressed in the equation:

o,H,N oo

As a Xanthin, this new body with chlorin-water gives a strong murexid reaction. It melts at from 127 to 128 centigrade. It is readily soluble in water, alcohol, chloroform, benzene, ether, and concentrated hydrochloric or sulfuric acid. From an aqueous solution this mass is precipitated by concentrated alkaline lyes as a colorless oil which soon solidifies to a crystalline mass.

3-methyl-chloro-Xanthin and the process of preparing it, while described for the purposes of a full disclosure, are not herein claimed, since they are covered in my Patent No. 631,757 aforesaid.

What I claim, and desire to secure by Letters Patent, is

1. The process which consists in submitting 3-alkyl-chloro-xanthin to the action of an alkylizing agent.

2. The process which consists in heating 3-methyl-chloro-Xanthin with potash-lye and alcohol, together with ethyl-iodid.

3. The process which consists in dissolving 3-methyl-chloro-Xanthin in potash -lye and alcohol, adding ethyl-iodid and boiling in a reflux cooler, all in the proportions and under the conditions substantially as stated.

4. The process which consists in subjecting 3-methyl-1-7-diethyl-2-6-dioxy-8-chloro purin to the action of a reducing agent.v

5. The process which consists in heating 3-methyl 1- 7-diethyl- 8- chloro-Xanthin to gether with hydriodic acid and phosphoniumiodid.

6. The process which consists in the following steps: heating 3 methyl- 1 7- diethyl=8- chloro-Xanthin together with fuming hydriodic acid in the proportions and temperature given; continuing the heating on a boilingwater bath and adding phosphonium-iodid I05 I g,

until a clear solution is formed, then evaporating this solution to dryness, taking up the crystalline residue with Water and supersaturating with alkali; then extracting with a suitable vehicle and evaporating the extract and, finally recrystallizing the colorless residue.

7. The process which consists in submitting 3-alkyl-chloro-Xanthin to an alkylizing agent and then acting upon the resultant trialkyl dioxy-chloro-purin with a reducing agent.

8; The process which consists in heating itated from an aqueous solution as a colorless 3-methyl-chloro-xanthin with potash-lye and oil bystrong alkaline lyes, which crystallizes alcohol together with ethyl-iodid and then in the form of vitreous, colorless prisms and treating the resultant product with hydriodic melts at about 127, centigrade.

5 acid and phosphoninm-iodid. In testimony whereof I aflix my signature I 5 9. As anew chemical compound, 3-methylin presence of two witnesses. 1-7-(1iethyl-2-6-dioxy-purin, having the' for- FRITZ ACH. mula above given, which is soluble in water, Witnesses: alcohol, chloroform, ether and concentrated LORENZ AGH, xo hydrochloric or sulfuric acid, which is precip- JACOB ADRIAN. 

